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Gene Expression Profiling of Human Adrenocortical Tumors Using Complementary Deoxyribonucleic Acid Microarrays Identifies Several Candidate Genes as Markers of Malignancy

Institut National de la Santé et de la Recherche Médicale, Equipe Mixte 01-05, Department of Cell Regulation and Dynamics, Commissariat à l’Energie Atomique (F.d.F., G.L.M., G.D., O.C., J.-J.F.), 38054 Grenoble, France; Departments of Integrative Biology (F.d.F.) and Endocrinology (O.C.) and Transcriptome Analysis Platform, Genopole Rhône-Alpes (M.E.A., F.B.), University Hospital of Grenoble, 38043 Grenoble, France; COMETE: The French Network for Studies on Human Adrenal Cortical and Medullary Tumors (F.d.F., N.C., G.L.M., G.D., J.B., X.B., P.-F.P., E.B., C.G., O.C., J.-J.F.), European Hospital Georges Pompidou, 75908 Paris, France; Institut National de la Santé et de la Recherche Médicale, Equipe de Recherche Méthodologique 02-06, University of Méditerranée (R.H.), 13288 Marseille, France; Department of Endocrinology, Cochin Hospital (J.B., X.B.), 75014 Paris, France; Department of Hypertension, European Hospital Georges Pompidou (P.-F.P.), 75908 Paris, France; Department of Endocrine Cancerology, Gustave-Roussy Institute (E.B.), 94805 Villejuif, France; and Laboratory of Functional Endocrine Explorations, Trousseau Hospital (C.G.), 75571 Paris, France

Address all correspondence and requests for reprints to: Dr. Jean-Jacques Feige, Institut National de la Santé et de la Recherche Médicale, Equipe Mixte 01-05, Department of Cellular Responses and Dynamics, Angiogenesis Laboratory, Commissariat à l’Energie Atomique Grenoble, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France. E-mail: jjfeige{at}cea.fr.

The aim of this study was to identify predictor sets of genes whose over- or underexpression in human sporadic adrenocortical tumors would help to identify malignant vs. benign tumors and to predict postsurgical metastatic recurrence. For this, we analyzed the expression of 230 candidate genes using cDNA microarrays in a series of 57 well-characterized human sporadic adrenocortical tumors (33 adenomas and 24 carcinomas). We identified two clusters of genes (the IGF-II cluster containing eight genes, including IGF-II, and the steroidogenesis cluster containing six genes encoding steroidogenic enzymes plus eight other genes) whose combined levels of expression appeared to be good predictors of malignancy. This predictive value was as strong as that of the pathological score of Weiss. The analysis of the population of carcinomas (13 tumors) for genes whose expression would be strongly different between recurring and nonrecurring tumors allowed identification of 14 genes meeting these criteria. Among these genes, there are probably new markers of tumor evolution that will deserve additional validation on a larger scale. Taken together, these results show that the parallel analysis of the expression levels of a selected group of genes on microgram quantities of tumor RNA (a quantity that can be obtained from fine needle aspirations) appears as a complementary method to histopathology for the diagnosis and prognosis of evolution of adrenocortical carcinomas.

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